Building better vaccines: how apoptotic cell death can induce inflammationand activate innate and adaptive immunity

The immunological consequences of apoptosis have been hotly debated. Apopto sis was originally described as a set of cellular morphological changes tha t occur in the absence of inflammation but the term has been redefined on t he basis of a set of conserved molecular events that include the activation of caspases. Though the apoptosis occurring during normal development is i mmunologically bland or even tolerizing, the apoptotic death after viral in fection or after the ligation of Fas can trigger powerful innate and adapti ve immune responses. The molecular machinery at the nexus of apoptosis and inflammation includes caspase-1 - an activator of 1L-1 beta and IL-18 - as well as the double-stranded-RNA-dependent protein kinase pathway and RNaseL pathway, which are key effecters of antiviral immunity. New proapoptotic v accines induce immune responses that may be able to prevent or treat infect ious disease and cancer.